Milk lipids are a principal source of cholesterol and saturated fat in the American diet. Research on the biosynthesis of milk lipids may afford a basis for controlling the kinds and amounts of lipids in milk. Further such research may provide insight into mechanisms of lipid accumulation, a biomedically important consideration in atherosclerosis obesity and various lipidoses. We are trying to understand how milk lipid precursors, including cholesterol, are transported from the blood into the lactating mammary cell and how the cell synthesizes, aggregates and secretes lipids. This necessarily renders understanding the structure and function of cell membranes an important part of the research objectives. Our research to date indicates that cholesterol and sphingomyelin, two lipids which tend to concentrate in the human atheromatous plaque, accumulate in the plasma membrane of the cell as a natural aging phenomenon. This membrane is suspect as an initial phase in the formation of atheroma. We wish to establish the molecular architecture and mode of formation of the plasma membrane. Transport of lipids will be investigated with the aid of radioactive tracer labeled metabolites and accepted techniques of isolating serum lipoproteins, the various cell membranes, appropriate fractions of milk, and the individual radioactive lipids in these fractions. Autoradiography will be used toward obtaining confirmatory evidence of lipid movement into, through and out of the cell. The sidedness of the milk fat globule, which exposes the outer surface of the plasma membrane and occludes the inner surface, will be used as an approach to membrane architecture. Various probes to label sites of the mebrane or to disintegrate it into fractions which may reveal fundamental molecular and enzymatic assciations will be employed and evaluated.